AB0815 CLINICAL PHENOTYPE AND ANTIBODY CORRELATIONS USING IMMUNOPRECIPITATION IN INDIAN PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHIES FROM THE MYOCITE COHORT
Authors: A. Loganathan, A. Rudge, H. Lu, E. Bowler, F. Mcmorrow, N. Ravichandran, A. K. Anuja, V. Agarwal, L. Gupta, N. Mchugh, S. Tansley
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> There is a lack of epidemiological studies in idiopathic inflammatory myositis (IIM) to identify geographical and clinical disease variations between populations. Reviewing disease prevalence in different populations and clinical presentations may help improve our understanding of rare diseases. <h3>Objectives</h3> We reviewed the clinic-serological profile of 148 patients from a well-characterised MyoCite cohort of juvenile and adult patients with IIM from Lucknow, India, to determine significant clinical characteristics associated with different myositis-specific antibodies (MSA). <h3>Methods</h3> The MyoCite cohort is a retro-prospective dataset of adult and juvenile IIM patients (2017 ACR/EULAR criteria or diagnosed by two rheumatologists) enrolled in Lucknow, India, between 2017-2020. (1) The cohort is well-characterised with a detailed case record form and glossary outlining clinical characteristics and disease outcomes with biospecimen archiving. Sera were shipped to the NMH lab in Bath, and autoantibody status was determined using immunoprecipitation (IP). Sera with 140kDa band were characterised for NXP2 versus MDA5 using ELISA. Clinical associations for specific autoantibodies on IP were analysed by comparing each MSA to the rest of the cohort. We conducted univariate and multivariate logistic regressions, with results reported as odds ratios with 95% confidence intervals (CI). We selected variables as candidates for the multivariate logistic regression which scored a p-value ≤0.3 in the univariate analysis. A stepwise procedure was to select the final multivariate models which achieved the best fit, measured using AIC. <h3>Results</h3> Of 148 patients, one had dual MSA antibody specificity (Jo1/NXP2) and was excluded from analysis. The median age of onset was 35.5, with 75.2% being women. Muscle weakness was present in 88.9% of patients; 61.5% had a rash consistent with dermatomyositis (DM), 35% were diagnosed with ILD, and 41.3% experienced arthritis. Underlying malignancy was present in 1.4% at the time of enrolment. Dermatomyositis (DM) (30%) was the most common subtype of IIM, followed by anti-synthetase syndrome (ARS) (20%), overlap myositis (16%) and juvenile DM (14%). Anti-Jo1 (10.9%) was the most common MSA detected, followed by MDA5 (9.5%) (figure 1), and 43.5% of patients were seronegative. Mechanic's hands were associated with anti-Jo1 (OR 20.5 95%CI 5-77.7) and ARS antibodies (OR 11.9 95%CI 3.8-36.9). Heliotrope rash (OR 6.4 95%CI 1.5-26.7) and gottron's sign (OR 5 95%CI 1.2-20.9) were associated with anti-MDA5 (Table 1). ARS antibodies were negatively associated with weakness and heliotrope rash. NXP2 was associated with dysphonia (OR 29.1 95%CI 3.5-243), while Mi2 was associated positively with a V-sign rash (OR 7 95%CI 1.4-34.7) and negatively with fever. SAE antibodies were associated with dysphagia (OR 9.3 95%CI 1.1-76.6). Seronegative IIM was associated with hyperpigmentation (OR 4.3 95%CI 1.6-11.7) and erythematous changes (OR 2.8 95%CI 1.2-6.5) and was negatively associated with arthritis and fatigue. <h3>Conclusion</h3> Autoantibodies are present in nearly two-thirds of Indian patients with IIM, commensurate with other populations (Figure 1), although the prevalence of individual MSA differs. The frequency of ILD is closer to those previously reported in European cohorts than in East Asian populations. Most MSAs exhibited association with prominent cutaneous manifestations, including mechanics hands, heliotrope rash, Gottron's sign, V-sign, hyperpigmentation and erythematous changes. These differences in antibody profile and clinical characteristics from the MyoCite cohort compared to that of different geographical and ethnic populations previously reported suggest the potential influence of genetics and/or environmental factors. <h3>References</h3> [1]Gupta L, Naveen R, Gaur P, Agarwal V, Aggarwal R. Myositis-specific and myositis-associated autoantibodies in a large Indian cohort of inflammatory myositis. Semin Arthritis Rheum. 2021;51(1):113-20 <h3>Acknowledgements</h3> BirdBath foundation. APLAR research grant. Ken Muirden Overseas Fellowship Grant, Arthritis Australia. <h3>Disclosure of Interests</h3> None Declared.